Vascular endothelial growth factor receptor 2-based DNA immunization delays development of herpetic stromal keratitis by antiangiogenic effects

Stromal keratitis (SK) is an immunoinflammatory eye lesion caused by HSV-1 infection. One essential step in the pathogenesis is neovascularization of the normally avascolar cornea, a process that involves the vascular endothelial growth Factor (VEGF) family of proteins. In this report, we targeted the proliferating vascular endothelial cells expressing VEGFR-2 in the SK cornea by immunization with recombinant Salmonella typhimurium containing a plasmid encoding murine VEGFR-2. This form of DNA immunization resulted in diminished angiogenesis and delayed development of SK caused by HSV-1 infection and also reduced augiogenesis resulting from corneal implantation with rVEGF. CTL responses against endothelial cells expressing VEGFR-2 were evident in the VEGFR-2-immunized group and in vivo CD8⁺ T cell depletion resulted in the marked redaction of the antiangiogenic immune response. These results indicate a role for CD8⁺ T cells in the antiangiogenic effects. Our results may also imply that the anti-VEGFR-2 vaccination approach might prove useful to control pathological ocular angiogetiesis and its consequences.